Renal Denervation Ameliorates Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury Through Regulating Mitochondria-Endoplasmic Reticulum Contact

Anatol J Cardiol. 2024 Jul;28(7):353-362. doi: 10.14744/AnatolJCardiol.2024.3579.

Abstract

Background: Myocardial ischemia-reperfusion injury (I/R) has been improved with drugs and effective reperfusion, but it still cannot be prevented.

Methods: To investigate whether renal denervation (RDN) reduces cardiomyocyte apoptosis by ameliorating endoplasmic reticulum stress, 60 male specific pathogen-free (SPF) Wistar rats were randomly divided into 6 groups (n = 6). We established the I/R rat model by ligating the left anterior descending artery. The I/R+ angiotensin receptor neprilysin inhibitors (ARNI) group received ARNIs for 2 weeks until euthanasia.

Results: The I/R+RDN and I/R+ARNI groups have significantly ameliorated left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) and reversed expansion of the left ventricular end-systolic diameter (LVSD) and left ventricular end diastolic diameter (LVDD) compared to the I/R group. The levels of norepinephrine (NE), angiotensin II, and aldosterone (ALD) increased significantly in the I/R group, but decreased significantly after RDN and ARNI intervention. In the I/R+RDN and I/R+ARNI groups, the myocardial tissue edema was alleviated. The infarct size was smaller in the I/R+RDN and I/R+ARNI groups compared to the I/R group. Apoptosis of cardiomyocytes and fibroblasts in myocardial tissue increased significantly in the I/R group, which was greatly diminished by RDN and ARNI. The expression of Bax, caspase-3, CHOP, PERK, and ATF4 protein was significantly increased in the I/R group, which compared to other groups, and the level of CHOP, PERK, and ATF4 gene expression increased. After RDN intervention, these expression levels recovered to varying degrees.

Conclusion: The effect of RDN may be associated with regulating the endoplasmic reticulum stress PERK/ATF4 signaling pathway.

MeSH terms

  • Animals
  • Apoptosis*
  • Denervation
  • Disease Models, Animal*
  • Endoplasmic Reticulum
  • Endoplasmic Reticulum Stress
  • Kidney* / innervation
  • Kidney* / pathology
  • Male
  • Mitochondria / metabolism
  • Myocardial Reperfusion Injury*
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / pathology
  • Random Allocation
  • Rats
  • Rats, Wistar*

Grants and funding

This study was supported by the National Natural Science Foundation of China (81970303).